Autophagy

Autophagy is a highly conserved catabolic process in which cells selectively self-digest their cytoplasmic components by forming a double-membraned vesicle around sequestered material, termed the autophagosome. Fusion with a lysosome generates an autolysosome which degrades and recycles material back to the cytoplasm. This process was first identified in yeast as a survival response to starvation and it is genetically regulated by a family of ATG genes, which have known homologues in humans.

In humans, constitutive autophagy is a necessary homeostatic process which removes damaged organelles and thus can be protective against cancer. However, when a cancer is established, autophagy takes on new roles and helps cancer cells to survive in growth limiting conditions such as low oxygen, low nutrient supply and absence of normal tissue specific survival signals. Autophagy can impact on immune recognition, dormancy, differentiation and stem cell biology.

Inducing excessive/deregulated autophagy may also be a major mechanism for killing cancer cells that have deleted normal cell death programs. Autophagic cell death has already been reported to be induced in several cancers by chemotherapeutics. In order to improve treatment of cancer, we need to better understand how to combat the survival functions of autophagy and induce a death process in cancer cells.